Cardiovascular Emergency Conference

Transcription

1 Cardiovascular Emergency Conference Acute Management of Stroke Patients 5 th April 2014 Dr Siva Seeta Ramaiah Consultant Neurologist Hospital Kuala Lumpur

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3 6 new stroke cases every hour

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5 Burden of Stroke Globally: 3rd common cause of mortality Leading cause of disability 5.7 millions death from developing countries Decreasing trend in developed countries Better prevention treatment and aftercare management Murray CJL et al Mathers CD et al Hamidon BB et al. 2002

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7 Burden of Stroke Malaysia top 5 leading causes of death Top 10 leading causes of hospitalization Loo KW et al. 2012

8 Burden of Stroke Loo KW et al. 2012

9 30 DAY MORTALITY (%) Ischemic VS Hemorrhagic Stroke: Incidence & Mortality INCIDENCE MORTALITY ISCHAEMIC STROKE HEMORRHAGIC STROKE %-37% 25% 20 75% 10 8%-12% 0 ISCHAEMIC STROKE HAEMORRHAGIC STROKE Hamidon BB et al. Neurology Asia 2003 American Heart Association Heart Disease and Stroke Statistics-2005 Update

10 Stroke & TIA definition Rapidly developing clinical neurological signs of focal (or global) disturbance of cerebral function, with symptoms lasting 24 hours or longer or leading to death, with no apparent cause other than of vascular origin TIA < 24 hrs WHO 1998

11 TIA- tissue definition transient ischemic attack (TIA): a brief episode of neurological dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting less than one hour, and without evidence of acute infarction Assessed by imaging- absence of end organ injury

12 Oxfordshire Community Stroke Project Classification (OCSP) Total Anterior Circulation Infarct (TACI) Partial Anterior Circulation Infarct (PACI) Posterior Circulation Infarct (POCI) Lacunar infarct (LACI)

13 50% 25% 20%

14 Differential diagnosis of stroke Metabolic/toxic encephalopathy (hypoglycaemia, HHS,Wernicke-Korsakoff syndrome, drug intoxication) Epileptic seizures (postictal Todd s paresis) Hemiplegic migraine Structural intracranial lesions ( e.g. subdural haematoma, brain tumour, AVM) Encephalitis (e.g. HS virus), brain abscess, TB Head injury Hypertensive encephalopathy Relapsing MS Conversion disorders Hyperviscosity syndrome Peripheral nerve lesions (e.g. GBS)

15 Vascular risk factors

16 Time is brain Typical MCA infarct: 2 million nerve cells are lost each minute If reperfusion has not been achieved

17 Stroke Recognition Aspirin ASAP Risk Factor control Neurosurgery Thrombolysis

18 General Supportive Care and Treatment I Stroke is a primary failure of focal tissue oxygenation and energy supply Systemic hypoxemia and hypotension should be avoided and, if present, corrected to limit further cellular damage AHA/ASA GUIDELINES 2013

19 General Supportive Care and Treatment II Cardiac monitoring is recommended to screen for AF and for at least the first 24 hours. Class I, LOE B Patients who have high BP but eligible for IV rtpa should have their BP carefully lowered so that their SBP is <185 mm Hg and their DBP is <110 mm Hg Class I, LOE B BP is stabilized at the lower level before treating with IV rtpa and maintained <180/105 mm Hg for at least the first 24 hrs after IV rtpa Class I, LOE B AHA/ASA GUIDELINES 2013

20 General Supportive Care and Treatment III Airway support and ventilatory assistance - decreased consciousness or who have bulbar dysfunction causing compromise of the airway. Class I, LOE C Supplemental oxygen should be provided to maintain oxygen saturation > 94%. Class I, LOE C Sources of hyperthermia (T >38 C) should be identified and treated with antipyretic Class I, LOE C AHA/ASA GUIDELINES 2013

21 General Supportive Care and Treatment Ⅳ If not thrombolysed- to lower BP by 15% during the first 24 hrs Consensus exists that medications should be withheld unless the SBP is >220 mm Hg or the DBP is >120 mm Hg. Class I, LOE C Hypovolemia - corrected with IV normal saline Cardiac arrhythmias that might be reducing cardiac output should be corrected. Class I, LOE C Hypoglycemia- should be treated to achieve normoglycemia Class I, LOE C AHA/ASA GUIDELINES 2013

22 General Supportive Care and Treatment of Acute Complications Antihypertensive- within 24 hrs of stroke is relatively safe. Restarting antihypertensive is reasonable after the first 24 hrs- pre-existing HPT and are neurologically stable. Class IIa, LOE B Management of HPT in patients not undergoing reperfusion strategies remains challenging as data inconclusive or conflicting. Patients who have malignant hypertension or other medical indications for aggressive treatment of BP should be treated accordingly. AHA/ASA GUIDELINES 2013

23 Recommendations for BP lowering in patients with AIS Ther Adv Chronic Dis July; 3(4):

24 REPERFUSION OF ISCHAEMIC BRAIN Core of infarct tissue might not be salvageable, adjacent dysfunctional tissue (ischaemic penumbra) might be saved if the circulation is restored and metabolism is normalized IV Thrombolysis With rt-pa IV rt-pa (0.9mg/kg, max. 90mg) - 10% bolus followed by a 60-mins infusion, within 4.5 hrs of onset of ischaemic stroke. (Level 1, Grade A)

25 Every 100 patients treated: 32 will have a better outcome 3 will have a worse final global disability outcome

26 rtpa 6 large RCTs NINDS (1 and 2) European Cooperative Acute Stroke Study (ECASS I and II) ATLANTIS A and B

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28 (ECASS 3) trial European Cooperative Acute Stroke Study A double-blind, placebo-controlled study of IVtPA, has demonstrated that IVtPA given between hours of stroke onset was significantly associated with a good clinical outcome (mrs score 0 to 1) compared with placebo with an acceptably low rate of (sich).

29 ECASS 3

30 For the types of patient recruited in IST-3, despite the early hazards, thrombolysis within 6 h improved functional outcome. Benefit did not seem to be diminished in elderly patients. International Stroke Trial [IST-3] Lancet patients were enrolled by 156 hospitals in 12 countries (1515 in the rt-pa group vs 1520 in the control group) 1617 (53%) were older than 80 years of age.

31 Adjusted odds ratio Time Dependency of Alteplase Effect Pooled analysis of individual patient data (n=2775) from 6 trials of i.v. alteplase vs placebo showed that the effective treatment window may extend to 4.5 hours OR 2.8 OR 1.5 OR OR h 3h 4.5h 6h OR, odds ratio Time Interval from onset of symptoms to treatment initiation [min] Hacke et al. Lancet 2004; 363:

32 Time is Brain Excellent outcome (mrs 0-1) n=3530 NNT Treatment effect p<0.001 Interaction with time p= hours Lees et al Lancet 2010

33 Indications for rt-pa

34 IV tpa contraindications? Too mild, rapidly improving, too severe? Symptoms suggestive of SAH despite normal CT Seizure at onset use advanced imaging BSL <2.7mmol/L Fix it then treat BP >185/110 Europe add: Age>80 diabetes + prior stroke Head trauma or prior stroke within 3 months Non-compressible arterial puncture within 7 days Any history of previous intra-cranial hemorrhage Evidence of active bleeding or acute trauma (fracture) on examination If on anticoagulation: warfarin+inr>1.7/heparin w/ abnormal APTT Platelets <100 Myocardial infarction within 3 months RELATIVE Contra-indications Gastrointestinal or genitourinary hemorrhage within 21 days Major surgery within 14 days CT >1/3 MCA hypodensity Weigh risk-benefit, d/w surgeon beyond our help IST-3

35 What about Asian patients?

36 Low dose vs standard dose tpa 0.6 mg/kg is the only approved dosage in Japan since 2005 Japan Alteplase Clinical Trial (J-ACT) J-ACT2 and Japan post-marketing Alteplase Registration Study (JMARS) SAMURAI register TTT- AIS (Taiwan)

37 Enhanced Control of Hypertension and Thrombolysis in Stroke Disease (ENCHANTED) Recently launched RCT study -to address 4 key questions : Whether low-dose tpa (0.6 mg/kg) is truly equivalent in efficacy, or even safer (low risk of SICH), to the standard dose (0.9 mg/kg), not just in Asians but around the world. Effect of intensive BP lowering on outcomes and the risk of SICH.

38 Can we do better than IV tpa? Site of occlusion Recanalization after-tpa* ICA terminus 5% MCA M1 30% MCA M2 42% Basilar 11% Overall 30% * Saqqur et al Stroke 2007 & Bhatia et al Stroke 2010

39 Intra-arterial thrombolysis (IAT) Option for the treatment of selected patients who have major stroke of <6 hours duration due to occlusions of the MCA/ ICA and carotid terminus who are not otherwise candidates for IV-rtPA. Level II-2, Grade C

40 The Interventional Management of Stroke (IMS III) phase 3, randomized, innovative design patients in whom IV t-pa administered within 3 hours after stroke onset were randomly assigned to receive IV t-pa alone (full dose) or IV t-pa (2/3 rd dose) followed by endovascular treatment.

41 (IMS III) Outcome: mrs score < 3 at 90 days (40.8% with endovascular therapy and 38.7% with IV t-pa; 95% [CI], 6.1 to 9.1 Mortality at 90 days: endovascular-therapy (19.1%) and IV t-pa groups (21.6%) P = 0.52

42 (IMS III)- Conclusions The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after IVt-PA, as compared with IV t-pa alone

43 362 patients with AIS within 4.5 hours after onset, to endovascular therapy (IAT with [t-pa], mechanical clot disruption or retrieval, or a combination of these approaches) or IV t-pa.

44 Local versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS Expansion) trial Outcome mrs score of 0 or 1 at 3 months;30.4% with endovascular treatment 34.8% with (IV t-pa) OR with endovascular treatment was 0.71 (95% CI, 0.44 to 1.14; P = 0.16)

45 (SYNTHESIS Expansion) The results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to standard treatment with intravenous t-pa * the median time from stroke onset to the start of treatment was 1 hour longer in the endovascular group than in the medical-therapy group

46 MR RESCUE Phase 2b, randomized, controlled, open-label, multicenter trial (22 study sites) in North America

47 MR RESCUE NIHSS score, 6 29; (ICA, M1, M2) assigned within 8 hrs to undergo either mechanical embolectomy or standard medical care (IV tpa) Pre-treatment CT/MR perfusion Randomization was stratified according to whether the patient had a favorable penumbral pattern (substantial salvageable tissue and small infarct core) or a non-penumbral pattern (large core or small or absent penumbra).

48 MR Rescue- methodology

49 MR RESCUE mean mrs scores did not differ between embolectomy and standard medical care (3.9 vs. 3.9, P = 0.99)

50 MR Rescue-conclusions A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for AIS nor was embolectomy shown to be superior to standard care.

51 What next? Tenecteplase- a genetically engineered mutant t-pa, was associated with significantly better reperfusion and clinical outcomes at 24 hours than alteplase Desmoteplase- DIAS 3/4 New endovascular devices- (stent retrievers) were significantly more effective than 1 st -generation devices for improving reperfusion and outcome at 90 days EXTEND IA ECASS-4 MR WITNESS

52 HKL Experience Service started in June 2013 Services offered from 8.00 am to 7.00pm daily Thrombolysis calls 33 (likely underestimate) Thrombolysed cases 12 patients Thrombectomy cases 1 patient

53 Summary of thrombolysed cases -Premorbid status CT F YZ A RM GS* ND * FM MF RS MA J KM M G Age Sex M F F M F F M M M M M M HTN DM + + Smoker + IHD + AF Old stroke + + Others Rena l Gout BA Mean age: 55.2 years Main R/F Hypertension (91.6%)

54 Summary of thrombolysed cases Time CT F YZ A RM * GS* ND ** FM MF RS MA J Time onset (H) (W) KM M G (W) 1130 Time arrival to ED (H) Time CT done (H) (1300) Door to CT (min) Time of diagnosis (H) Time tpa started (H) Door to needle (min) Onset to needle (min) mrs at 3 months/ *discharge * 4 * 3 6 1

55 Summary of thrombolysed cases Outcome on discharge / 3months post stroke mrs 0 mrs 1 mrs 2 mrs 3 mrs 4 mrs 5 mrs 6

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57 Summary of thrombolysed cases Best Worst Mean Median Door to CT (min) Door to Needle (min) Onset to Needle

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59 False Alarm Reasons Number of cases Intracranial bleeding 10 NIHSS too good (<4) or too severe (>22) 4 Thrombolysis call after 7pm 2 Stroke mimics 3 Technical problem 1 Poor premorbid mrs/age 80 years 2

60 Case scenario 1 55/Punjabi/Man HPT- presented L sided weakness and slurred speech at 7.30am Arrival A+E 9.15 am CT brain 9.30 am O/e; Visual neglect / Hand grip 2/5 hip/ shoulder and elbow 4+ *(NIHSS 8) CT brain- NAD Thrombolysed 81.9 mg (alteplase) at am

61 D2 post tpa D3 post tpa

62 Case scenario 1 Post thrombolysis NIHSS 2 (D2 stroke) D2 CT haemorrhagic transformation- aspirin withheld GCS dropped 13/15 repeat CT worsening haemorrhagic transformation referred neurosurgical treated conservatively. 08/10/13- developed calf pain with swelling U/SS confirmed Left DVT Started clexane 0.6 ml bd and warfarin on D12 Discharged D15 NIHSS discharge 1 mrs 1

63 Case scenario 2- Utility of CTP 58 years man Indian man, with no known medical illness. Presented with sudden onset of inability to talk upon waking up on the day of admission at 845 am associated with mild right sided body weakness. Last seen well at 12 am the night before. He presented to ED at around 1015 am. His NIHSS score was 8 on arrival, subsequently deteriorated to 10. He had partial right gaze palsy, marked expressive aphasia, right facial weakness, right hemiparesis with power of 4+/5.

64 His initial CT brain noted left MCA dense cord sign, with no early ischemic changes CTA were done at 1.00pm (4hour 15 min after wake up stroke)

65 CTP were done at 1.00pm (4 hours 15 mins after wake up stroke) and noted perfusion mismatch

66 Case scenario 2- Progress He was in fast AF (HR ~170/min) with heart failure and bibasal lungs crackles. After stabilization of his HR and pulmonary oedema, decision made for tpa thrombolysis at 2.30 pm (4 hour 30 min after wake up stroke) and NIHSS score 11 before infusion. After thrombolysis, he was warded in CRW. Echo shows EF of 20%. Heart failure and rate controlled were subsequently achieved. His NIHSS score has improved to 4 (day 2), 2(day 3) and 0 ( day 4) Dabigatran 150 mg bd started on D7

67 MRI DWI and ADC showed diffusion restriction in left parietal regions on day 3 Repeated CT brain on day 6 showed only small infarct in left corona radiata.

68 Case scenario 3 Intra-arterial therapy 62/M/Malay Underlying DM/HPT/CKD/Old PTB with bronchiectasis and Hx of CVA 1 st episode Jan 2013 and 2 nd episode June 2013 Onset am, R sided weakness and inability to talk. Arrival ED 1pm. Seen Neuro 1.10 pm-bp 160/95, NIHSS 23, GCS 10 (global aphasia), L gaze paresis, Visual field defect, Power R side 0/5 with normal Left UL and LL. CT done 1.25pm. Ct brain- loss of grey white matter differentiation L MCA. Not thrombolysed due to relative contraindications: #recurrent stroke (last stroke in June 2013) #NIHSS 23 #> 1/3 early loss of grey white matter differentiation in Left MCA

69 1 st CT Brain early loss of grey white matter differentiation in Left MCA

70 DSA done left M1/M2 junction occlusion Post retrieval DSA complete recanalization.

71 1 hour post clot retrieval 5 hours post clot retrieval

72 Case scenario 3 IAT Called Intervention team for possible IAT Wife consented for clot retrieval 4pm- DSA done left M1/M2 junction occlusion. R CFA Solitaire AB used to retrieve the occlusion. Post retrieval DSA complete recanalization. Ct Brain repeat at 5pm shows reperfusion bleed at L MCA region with perilesional edema. Admitted to HDU for close monitoring of BP and GCS ( NO ICU bed) GCS dropped 8 pm 5/15- intubated and ventilated in HDW, repeat CT Brain shows Left MCA territory bleed with extensive edema and mass effect. Left decompressive craniectomy done 18/09/13@ Brain very tense and noted brain herniating out through dural slit Deteriorated next day

73 Thank You Dr Siva Seeta Ramaiah Neurologist Department of Neurology Hospital Kuala Lumpur

74 Acknowledgement Dato Dr Md. Hanip bin Rafia Neurology Department HKL Casualty Department- HKL Radiology Department- HKL Neurosurgical Department- HKL Anesthesiology Department HKL All HKL Staff